OBJECTIVE: To explore the genetic basis of a patient suspected for Loeys-Dietz syndrome (LDS). METHODS: A adult male patient with aneurysmal dilation of the aortic root identified during the treatment for chronic myeloid leukemia at Anzhen Hospital of Capital Medical University in 2021 was selected as the study subject. Clinical data of the patient were retrospectively collected. Peripheral blood samples were collected from the patient and his family members and subjected to whole-exome sequencing (WES). Candidate variant was verified by bioinformatic analysis, with a focus on the genes associated with hereditary aortic aneurysms. Candidate variant was validated by Sanger sequencing. The online SpliceAI software was used for the prediction of protein function. The results, combined with information from public databases, were used to classify the pathogenicity of the candidate variant according to the guidelines from the American College of Medical Genetics and Genomics (ACMG). This study was approved by the Ethics Committee of Beijing Anzhen Hospital (Ethics No. 2023163X). RESULTS: Imaging analysis revealed that the patient had aneurysmal dilation of the aortic root. Based on his clinical features and past history, a provisional diagnosis of LDS was established. WES revealed that the patient had harbored a heterozygous splice site variant c.206+2T>G in the SMAD3 gene (NM_005902). The variant was not reported in public databases and was predicted to be pathogenic by SpliceAI. Sanger sequencing showed that the variant was also present in the proband's mother, sister, nephew, and daughter, but not in his father. Based on the guidelines from the ACMG, the variant was classified as likely pathogenic (PVS1+PM2_Supporting). CONCLUSION The heterozygous splice site variant c.206+2T>G of the SMAD3 gene probably underlay the disease in this patient. Above discovery has enriched the mutational spectrum of LDS, which may facilitate delineation of the genotype-phenotype correlation and provide a basis for further risk stratification and personalized treatment of LDS.
Adult ; Humans ; Male ; Exome Sequencing ; Loeys-Dietz Syndrome/genetics* ; Mutation ; Pedigree ; Smad3 Protein/genetics*

OBJECTIVE: To summarize the clinical features and spectrum of genetic variants in 12 patients with Loeys-Dietz syndrome (LDS), and to explore the correlation between the type of genetic variants and clinical phenotypes. METHODS: Twelve patients suspected for LDS at Beijing Anzhen Hospital Affiliated to Capital Medical University from January 2015 to January 2022 were selected as the study subjects. Clinical data of the patients were collected. Genomic DNA was extracted from peripheral blood samples and subjected to genetic testing. Pathogenicity of candidate variants was analyzed. RESULTS: The clinical phenotypes of the 12 patients have mainly included cardiovascular, musculoskeletal, craniofacial, skin, ocular and other systemic signs. Four patients (patients 5-1, 5-2, 6, 7) have carried heterozygous missense variants of the TGFBR1 gene, 5 patients (patients 1-1, 1-2, 2, 3, 4) have carried heterozygous variants of the TGFBR2 gene, and 2 patients (patients 8-1, 8-2) had carried heterozygous frameshift variants of the TGFB3 gene. One patient (patient 9) had carried a heterozygous missense variant of the SMAD3 gene. Among these, TGFBR1 c.603T>G (p.1201M) and TGFB3 c.536delA (p.H179FS35) had not been reported previously. CONCLUSION Variants of the TGFBR1, TGFBR2, SMAD3, TGFB2, TGFB3 and SMAD2 genes are mainly associated with LDS. The severity of the disease phenotype caused by the same variant may vary, whilst the clinical phenotype caused by different variant sites may be specific.
Humans ; Loeys-Dietz Syndrome/genetics* ; Receptor, Transforming Growth Factor-beta Type I/genetics* ; Receptor, Transforming Growth Factor-beta Type II/genetics* ; Transforming Growth Factor beta3 ; Face

OBJECTIVE: To explore the genetic basis of a patient with clinically suspected Loeys-Dietz syndrome (LDS). METHODS: A child who had presented at Beijing Anzhen Hospital in September 2018 was selected as the study subject. Clinical data and family history of the patient were collected, along with peripheral blood samples of the proband and his parents. Whole exome sequencing (WES) was carried out through next-generation sequencing. RESULTS: Candidate variants were searched through bioinformatic analysis focusing on genes associated with hereditary aortic aneurysms. Candidate variant was verified by Sanger sequencing. The patient was found to have cardiovascular abnormalities including early-onset aortic dilatation and coarctation, and LDS syndrome was suspected. WES revealed that he has harbored a heterozygous c.1526G>T missense variant of the TGFBR2 gene. The same variant was not found in either parent and was predicted as likely pathogenic (PM1+PM2_Supporting+ PM6+PP3+PP4) based on the guidelines from the American College for Medical Genetics and Genomics (ACMG). CONCLUSION The TGFBR2 c.1526G>T variant probably underlay the LDS in this patient and was unreported previously in China. Above finding has enriched the mutational spectrum of the TGFBR2 gene associated with the LDS and provided a basis for the genetic counseling for the patient.
Child ; Humans ; Male ; China ; Computational Biology ; Family ; Loeys-Dietz Syndrome/genetics* ; Mutation ; Receptor, Transforming Growth Factor-beta Type II/genetics*

Aneurysm, Dissecting/complications* ; Coronary Artery Disease/complications* ; Dyspnea/complications* ; Humans ; Syncope/etiology*

Objective: To investigate the prognosis factors for death within 90 days after discharge in patients with acute kidney injury(AKI) treated requiring continuous renal replacement therapy(CRRT) undergoing surgery for acute Standford type A aortic dissection. Methods: The clinic data of 126 patients undergoing CRRT for postoperative AKI after acute type A aortic dissection surgery in the Center for Cardiac Intensive Care, Beijing Anzhen Hospital from July 2016 to February 2019 were analyzed retrospectively. There were 83 males and 43 females, aging (52.9±11.2) years(range: 25 to 70 years). The patients' demographic characteristics, disease-related information, perioperative data, laboratory indexes during CRRT, complications, and survival information within 90 days after discharge were recorded. Independent prognosis factors for death within 90 days of discharge were determined by Kaplan-Meier survival analysis, univariate and multifactorial Cox regression analysis. Results: Totally 57 of 126 patients(45.2%) died over the first 90 days after discharge. Kaplan-Meier survival analysis and univariate Cox regression analysis showed that there were significant differences between the non-survival and survival group including ≥65 years old, high lactate values 12 hours after CRRT, pulmonary infection, liver dysfunction, presence of permanent neurological complications, and postoperative ejection fraction(EF)<45%. Multifactorial Cox regression analysis revealed that ≥65 years old(HR=2.14, 95%CI: 1.09 to 4.21, P=0.03), high lactate values 12 hours after CRRT(HR=1.13, 95%CI: 1.06 to 1.20, P=0.01) and postoperative EF<45%(HR=2.21, 95%CI: 1.09 to 4.51, P=0.03) were independent prognosis factors for patients' death within 90 days after hospital discharge. Conclusions: ≥65 years old, high lactate values 12 hours after CRRT and postoperative EF<45% are independent prognosis factors for death within 90 days after discharge in patients undergoing CRRT for AKI after acute type A aortic dissection surgery. Proper identification and management of prognosis factors could be beneficial to improve patients' outcomes.
Acute Kidney Injury/therapy* ; Aged ; Aneurysm, Dissecting/surgery* ; Continuous Renal Replacement Therapy ; Female ; Humans ; Lactates ; Male ; Patient Discharge ; Prognosis ; Renal Replacement Therapy/adverse effects* ; Retrospective Studies ; Risk Factors

Carotid arterial dissections may result from spontaneous or traumatic causes. Postcoital arterial dissections have been reported in both the vertebral and coronary arteries. We report a rare case of spontaneous dissection on the extracranial internal carotid artery in a Filipino female after sexual intercourse, leading to a fulminant middle cerebral artery (MCA) territory infarct. Although postcoital carotid artery dissection is a very rare cause of neck vessel dissections, its rapid progressive course can lead to massive cerebral infarction and prompt management must be initiated.
Cerebral Infarction ; Carotid Artery, Internal, Dissection

Objective: To investigate the effect of bare-metal stent related technique on distal aortic dissection involving abdominal visceral segment. Methods: A retrospective analysis was performed on clinical data of 33 patients with distal aortic dissection involved abdominal visceral segment, who hospitalized in the Vascular Surgery Department of Shanghai Changhai Hospital from July 2012 to September 2019. The effect of the treatment was evaluated according to the clinical and preoperative, intraoperative and follow-up imaging data derived from (aorta computed tomography angiography (CTA) and digital subtraction angiography (DSA)) as well as the changes of the maximal diameter of the aorta and the thrombosis of the false lumen of the dissection. The criteria were as follows: the maximum diameter change of aortic dissection<5 mm was defined as stable; the maximum diameter decrease of aortic dissection≥5 mm was defined as effective reduction; the maximum diameter increase of aortic dissection≥5 mm was defined as expansion; the definition of diameter change of false lumen was the same as above. The hospital complications, clinical symptoms and survival were recorded. Results: There were 28 male patients in this cohort, the mean age was (57.6±4.9) years old. Twenty-one patients were treated with bare-metal stent and coils technique, of which 8 patients were jointly treated with stent grafts. Twelve patients were treated with multi-layer bare-metal stent technique, of which 4 patients were jointly treated with stent grafts. Intraoperative DSA image results showed that the visceral arteries were patent during the treatment, and the blood flow velocity of the false lumen was reduced in all 33 patients. There were no adverse events such as distal outflow tract embolism and coil displacement during the operation. During the period of hospitalization, one patient developed intimal rupture of subrenal abdominal aortic dissection on the fourth day after operation and emergency endovascular graft exclusion was performed for abdominal aortic dissection, and the patient recovered well from the emergency operation. The follow-up time was (16.7±14.0) months. One patient died 1 year after surgery due to non-disease-related factors. Follow-up CTA imaging results showed that the maximum diameter of the aorta in abdominal visceral segment tended to be smaller ((39.1±13.4) mm vs. (41.3±11.9) mm, P=0.469), and the maximum diameter of the false lumen was significantly reduced ((16.2±12.9) mm vs. (23.5±10.7) mm, P=0.014). The maximum diameter of the aortic dissection was reduced in 12 cases, stable in 19 cases, expanded in 2 cases. The maximum diameter of the false lumen was effectively reduced in 22 cases, stable in 10 cases, and expanded in 1 case. Four patients developed small endoleak in the false lumen, one of them was nearby the renal artery stent, and the remaining patients experienced complete thrombosis of the false lumen. Conclusions: Endovascular treatment of distal aortic dissection involving abdominal visceral segment with bare-metal stents related technique could promote the shrink and the thrombosis of the false lumen, and slow down the blood flow from the tear into the false lumen in the setting of patency of visceral arteries.
Aneurysm, Dissecting/surgery* ; Aortic Aneurysm, Thoracic/surgery* ; Aortography ; Blood Vessel Prosthesis Implantation ; China ; Endovascular Procedures ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Stents ; Treatment Outcome

Objective: To explore the clinical implication of tissue-related biomarkers in patients with acute aortic dissection (AAD). Methods: It was a cross-sectional study. Ten Stanford Type A AAD patients, who were diagnosed and surgically treated in the Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, from December 2018 to August 2019, were selected as the case group. Meanwhile, 10 patients with atherosclerotic heart disease, who underwent coronary artery bypass grafting (CABG), were selected as control group. The ascending aorta tissue specimens from patients of the two groups were collected during the operation. Four-dimensional non-standard quantitative proteomics technology (4D-LFQ) was used to detect the protein profile of ascending aorta tissue specimens of the two groups and to screen out differentially expressed proteins and analyze their biological functions. Precise quantification of the selected target proteins was achieved by parallel response monitoring (PRM). Results: A total of 3 985 proteins were identified by 4D-LFQ technology, among which 3 350 proteins could be quantified. There were 39 proteins were significantly upregulated and 47 proteins were significantly downregulated in AAD group. The results of biological function analysis showed that most of the differentially expressed proteins were located in the extracellular, and their functions were mainly involved in cell migration and proliferation, inflammatory cell activation, cell contraction, and muscle organ development. The 15 selected proteins underwent precise quantification by PRM, and the results showed that integrin α-Ⅱb (ITGA2B), integrin α-M (ITGAM), integrin β-2 (ITGB2), integrin β-3 (ITGB3) were significantly upregulated in the ascending aorta tissue of AAD patients. Conclusion: ITGA2B, ITGAM, ITGB2, and ITGB3 are highly expressed in aortic tissues of patients with AAD, which may be used as biomarkers for the diagnosis of AAD patients.
Aneurysm, Dissecting ; Aorta ; Biomarkers ; Coronary Artery Bypass ; Cross-Sectional Studies ; Humans

OBJECTIVE: To explore the genetic basis for a patient with aortic root aneurysm and valve insufficiency. METHODS: The patient was subjected to whole exome sequencing (WES) with a focus on the analysis of genes related to aortic aneurysm and other genetic diseases involving the cardiovascular system. Suspected pathogenic site was validated by Sanger sequencing of the patient and his family members. RESULTS: WES has revealed a heterozygous c.830T>C variant (NM_001130916.3) in the patient, which was not detected among healthy members of his family. SIFT, PolyPhen2 and Mutation Taster predicted the variant to be disease causing, resulting in destruction of the structure and function of the TGFBR1 protein. Based on the American College of Medical Genetics and Genomics (ACMG) guidelines, the variant was predicted to be likely pathogenic (PM1+PM2+PM6+PP3+PP4). CONCLUSION The c.830T>C variant of the TGFBR1 gene probably underlay the disease in the proband. Above finding has enriched the spectrum of TGFBR1 gene variants in Chinese population.
China ; Echocardiography ; Humans ; Loeys-Dietz Syndrome/genetics* ; Mutation ; Pedigree ; Receptor, Transforming Growth Factor-beta Type I/genetics* ; Whole Exome Sequencing

Acute Disease ; Aneurysm, Dissecting/therapy* ; Aortic Aneurysm/complications* ; China ; Consensus ; Coronary Angiography ; Coronary Artery Disease/therapy* ; Humans